Hydrochloric Acid → Tert-butyl 4-[4-(4-{bis[(2,2,2-trichloroethoxy)carbonyl]amino}-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate

HRID 1744122Notes

Reaction equation

HRID 1744122 reaction equation
[NH2:1][C:2]1[C:3]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)=[CH:9][CH:8]=2)=[N:4][O:5][N:6]=1.Cl[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28].[ClH:35]>CN(C1C=CN=CC=1)C.ClCCCl>[Cl:32][C:31]([Cl:34])([Cl:33])[CH2:30][O:29][C:27]([N:1]([C:27]([O:29][CH2:30][C:31]([Cl:33])([Cl:32])[Cl:35])=[O:28])[C:2]1[C:3]([C:7]2[CH:8]=[CH:9][C:10]([N:13]3[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:17][CH2:18]3)=[CH:11][CH:12]=2)=[N:4][O:5][N:6]=1)=[O:28]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 870632,2,2-Trichloroethyl chloroformate3×HCID 22235822Tert-butyl 4-[4-(4-amino-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate

Product 1

HCID 22236059Tert-butyl 4-[4-(4-{bis[(2,2,2-trichloroethoxy)carbonyl]amino}-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst3×HCID 111,2-DichloroethaneSolvent

Procedure

To tert-butyl 4-[4-(4-amino-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate (700 mg, 2.03 mmol) and DMAP (820 mg, 6.7 mmol) in 1,2-dichloroethane (50 mL) under dry nitrogen was added 2,2,2-trichloroethyl chloroformate (0.62 mL, 4.5 mmol) dropwise and the reaction was refluxed for ½ hour. An additional aliquot of DMAP (820 mg, 6.7 mmol) and 2,2,2-trichloroethyl chloroformate (0.62 mL, 4.5 mmol) were added and the reaction mixture was refluxed for 1 hour. Further aliquots of DMAP (820 mg, 6.7 mmol) and 2,2,2-trichloroethyl chloroformate (0.62 mL, 4.5 mmol) were added and the reaction mixture was refluxed for a total of 4 hours. After cooling to rt, the reaction was poured into aqueous 10% HCl and the product extracted with EtOAc (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 3/7, then 1/1) to afford tert-butyl 4-[4-(4-{bis[(2,2,2-trichloroethoxy)carbonyl]amino}-1,2,5-oxadiazol-3-yl)phenyl]piperazine-1-carboxylate.

Workup

  1. temperaturethe reaction was refluxed for ½ hour
  2. temperaturethe reaction mixture was refluxed for 1 hour
  3. temperaturethe reaction mixture was refluxed for a total of 4 hours
  4. extractionthe product extracted with EtOAc (2×)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography over silica gel (EtOAc/Hex, 3/7

Sources & evidence

ORD record
ord-b5b69d6185374e9080a9a4e2e2d0c181
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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